Single nucleotide polymorphisms (SNPs) represent an abundant and useful source of genetic markers to understand complex diseases. SNPs in coding regions (cSNPs) of biologically important genes are likely to functionally alter the protein product. We have investigated the variability in DNA sequence in 40 genes related to cancer including oncogenes, tumor suppressor genes, and genes involved in cell cycle control. Primer pairs amplifying each exon and intron boundary were designed and used to amplify DNA from four European Americans (CEPH family parents), four African Americans, and four Asian American samples. Analysis of the products showed that over 90% produced a correctly sized product. The products were analyzed for variation by denaturing high performance liquid chromatography (DHPLC). A total of 42 potential variants were detected and the SNP was detected by sequencing in 35 cases. To confirm the segregation of these variants several of them were examined in entire CEPH pedigrees. We demonstrated that the variants did segregate along with flanking microsatellite markers. In total we scanned about 70 kb of sequence and found a nucleotide diversity of 2.5 X 10-5. This figure agrees with that reported in the literature for other genes using either DNA chip or DHPLC (1.7-3.1 X 10-5). Therefore DHPLC is an effective method to identify variations in genes that can then be used as genetic markers in population based studies. - Cancer genetics, Human Genetics, Tumor suppressor genes, - Human Tissues, Fluids, Cells, etc.